PO.BCS01.10 · 生物信息与计算
一个可扩展的、覆盖全蛋白质组的蛋白质分析平台，可对1000种蛋白进行绝对定量，助力肿瘤学药物发现流程
A scalable, proteome-wide protein profiling platform with absolute quantification of 1000 proteins to power oncologic drug discovery pipelines
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
蛋白质组学一直受到灵活性不足、成本高昂及定量不一致的制约。我们提出Omni 1000，一种由nELISA技术驱动的定量1000重解决方案——专为广泛、可重复且经济高效的蛋白质测量而设计。Omni 1000提供0.1 pg/mL的灵敏度、99.99%的特异性以及跨越3-6个数量级的动态范围。凭借<10%的CV，Omni 1000确保了发现与转化应用的精确性。
Omni 1000的内容通过严谨的、数据驱动的策略开发，以实现全蛋白质组范围的全面覆盖，同时保留高价值标志物。其基础由两个来源构建：（1）一组精选的最有价值蛋白（MVPs）——基于其在关键信号通路、转化研究及经验证终点中的普遍性而启发式选取的生物标志物；以及（2）具有疾病关联性的大规模高重蛋白质组数据集。为进行优化，我们应用最小冗余最大相关（mRMR）来减少重叠，通过重构损失最小化来保留高维数据集中的信号，并优先考虑MVPs。每次迭代均针对关键生物学本体进行验证——实现了92%的MVP覆盖率、100%的Reactome level 0、>80%的Reactome level 1、100%的药学相关KEGG信号通路及100%的MeSH疾病类别。
对于生物标志物发现，Omni 1000通过显著的成本效益及借助流式细胞术的快速读出，使大规模且临床相关的研究得以常规实现。在一项血浆生物库样本研究中，Omni 1000的使用成功展示了在临床症状发作前检测活动性类风湿关节炎免疫特征的早期洞见。
此外，Omni 1000的高通量能力被用于支持一个基于患者来源肿瘤类器官的药物筛选平台。Omni 1000的使用展示了关于基线供者异质性以及针对患者组织特征的药物化合物应答与耐药的洞见，这是推进精准医学的一项努力。
总之，我们展示了一种新颖的1000重解决方案Omni 1000，其内容在关键靶点与生物学广度之间取得平衡，并通过两个关键应用——疾病早期检测与高通量药物开发——展示了其实际应用价值。
查看英文原文 English abstract
Proteomics has been constrained by flexibility, high costs, and inconsistent quantification. We present Omni 1000, a quantitative 1000-plex solution powered by nELISA technology-designed for broad, reproducible, and cost-effective protein measurement. Omni 1000 delivers 0.1 pg/mL sensitivity, 99.99% specificity, and dynamic range spanning 3-6 logs. With <10% CV, Omni 1000 ensures precision for discovery and translational applications.
Omni 1000 content was developed through a rigorous, data-driven strategy to achieve comprehensive proteome-wide coverage while retaining high-value markers. The foundation is built from two sources: (1) a curated set of Most Valuable Proteins (MVPs)-biomarkers selected heuristically based on prevalence in key signaling pathways, translational research, and validated endpoints; and (2) large-scale, high-plex proteomic datasets with disease-association. To optimize, we applied Minimum Redundancy Maximum Relevance (mRMR) to reduce overlap, reconstruction loss minimization to preserve signal from high-dimensional datasets, and prioritized MVPs. Each iteration was validated against key biological ontologies-achieving 92% MVP coverage, 100% Reactome level 0, >80% Reactome level 1, 100% pharma-relevant KEGG signaling pathways, and 100% MeSH disease classes.
For biomarker discovery, Omni 1000 makes large-scale and clinically relevant studies routinely achievable through significant cost-efficiencies and rapid readout with flow cytometry. In a study of plasma biobank samples, use of Omni 1000 successfully demonstrated early insights in detecting active rheumatoid arthritis immune signatures prior to onset of clinical symptoms.
In addition, Omni 1000's high-throughput capabilities were used to support a drug screening platform based on patient-derived tumor organoids. Use of Omni 1000 demonstrated insights on baseline donor heterogeneity and drug compound responses and resistances specific to patient tissue profiles, an effort to advance precision medicine.
Together, we demonstrate a novel 1000-plex solution, Omni 1000, with content balancing critical targets and biological breadth, and demonstrate real-world utility through two key applications: early detection of disease and high throughput drug development.
利益披露 Disclosure
J. Robinson, None..
N. Robichaud, None..
G. Ongo, None..
K. Edwardson, None..
A. Rosenbloom, None..
N. Rashidi, None..
A. Tavakoli, None..
J. Munzar, None..
M. Dagher, None.